• Home
  • Search Results
  • TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells.

TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells.

The FEBS journal (2019-05-24)
Katia Schoeler, Andreas Aufschnaiter, Simon Messner, Emmanuel Derudder, Sebastian Herzog, Andreas Villunger, Klaus Rajewsky, Verena Labi

Upon activation by antigen, B cells form germinal centres where they clonally expand and introduce affinity-enhancing mutations into their B-cell receptor genes. Somatic mutagenesis and class switch recombination (CSR) in germinal centre B cells are initiated by the activation-induced cytidine deaminase (AID). Upon germinal centre exit, B cells differentiate into antibody-secreting plasma cells. Germinal centre maintenance and terminal fate choice require transcriptional reprogramming that associates with a substantial reconfiguration of DNA methylation patterns. Here we examine the role of ten-eleven-translocation (TET) proteins, enzymes that facilitate DNA demethylation and promote a permissive chromatin state by oxidizing 5-methylcytosine, in antibody-mediated immunity. Using a conditional gene ablation strategy, we show that TET2 and TET3 guide the transition of germinal centre B cells to antibody-secreting plasma cells. Optimal AID expression requires TET function, and TET2 and TET3 double-deficient germinal centre B cells show defects in CSR. However, TET2/TET3 double-deficiency does not prevent the generation and selection of high-affinity germinal centre B cells. Rather, combined TET2 and TET3 loss-of-function in germinal centre B cells favours C-to-T and G-to-A transition mutagenesis, a finding that may be of significance for understanding the aetiology of B-cell lymphomas evolving in conditions of reduced TET function.

Product Number
Product Description

2-Mercaptoethanol, for molecular biology, suitable for electrophoresis, suitable for cell culture, BioReagent, 99% (GC/titration)
Trypsin-EDTA solution, 10 ×, sterile-filtered, BioReagent, suitable for cell culture, 5.0 g porcine trypsin and 2 g EDTA, 4Na per liter of 0.9% sodium chloride
L-Glutamine solution, 200 mM, solution, sterile-filtered, BioXtra, suitable for cell culture
Lipopolysaccharides from Escherichia coli O55:B5, purified by phenol extraction
Aluminum potassium sulfate dodecahydrate, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5%
Corning® 96 Well EIA/RIA Assay Microplate, flat bottom clear, polystyrene, high binding surface, pkg of (individually wrapped), non-sterile, lid: no